Differential regulation and role of interleukin-1 receptor associated kinase-M in innate immunity signaling
| Autor: | Qifa Xie, Jianmin Su, Ingred Wilson, Liwu Li |
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| Rok vydání: | 2007 |
| Předmět: |
MAPK/ERK pathway
p38 mitogen-activated protein kinases Phosphatase Active Transport Cell Nucleus Cell Cycle Proteins Biology p38 Mitogen-Activated Protein Kinases Article Immediate-Early Proteins Lipopeptides Mice Protein Phosphatase 1 Phosphoprotein Phosphatases Animals Humans Extracellular Signal-Regulated MAP Kinases Receptor Cells Cultured Cell Nucleus Innate immune system Kinase Macrophages JNK Mitogen-Activated Protein Kinases Models Immunological Wild type Dual Specificity Phosphatase 1 IRAK1 Cell Biology Immunity Innate Cell biology Enzyme Activation Interleukin-1 Receptor-Associated Kinases Leukocytes Mononuclear Protein Tyrosine Phosphatases Peptides Signal Transduction |
| Zdroj: | Cellular Signalling. 19:1596-1601 |
| ISSN: | 0898-6568 |
| Popis: | Toll-like-receptor mediated signaling is finely regulated by a complex intracellular protein network including the interleukin-1 receptor associate kinases (IRAKs). IRAK-4, 1, and 2 may positively regulate innate immunity signaling through the activation of various downstream kinases such as MAPKs. In contrast, IRAK-M plays an inhibitory role through unknown mechanism. In this report, we show that IRAK-M is ubiquitously present in the cell, and becomes exclusively cytoplasmic upon bacterial lipoprotein Pam(3)CSK(4) challenge. Furthermore, using bone marrow derived macrophages (BMDM) from wild type, IRAK1(-/-), and IRAK-M(-/-) mice, we have herein demonstrated that IRAK-M selectively attenuates bacterial lipopeptide Pam(3)CSK(4)-induced p38 activation, but not ERK or JNK. IRAK1(-/-) and IRAK-M(-/-)BMDM display distinct activation profile of various MAP kinases upon Pam(3)CSK(4) challenge, indicating that IRAK-M exerts its inhibitory effect through an IRAK1 independent pathway. Pam(3)CSK(4) challenge leads to rapid decrease of MKP-1 protein level in IRAK-M(-/-)BMDM as well as THP-1 cells with decreased IRAK-M expression through siRNA interference. Our findings indicate that IRAK-M selectively attenuates p38 activation and inhibits innate immunity through stabilizing MKP-1. |
| Databáze: | OpenAIRE |
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